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New QSAR Models to Predict Human Transthyretin Disruption by Per- and Polyfluoroalkyl Substances (PFAS): Development and Application
Developmental Exposures to Three Mammalian Teratogens Produce Dysmorphic Phenotypes in Adult Caenorhabditis elegans
Recent Trends and Challenges on the Non-Targeted Analysis and Risk Assessment of Migrant Non-Intentionally Added Substances from Plastic Food Contact Materials
Application of a Dynamic Exposure Population Toxicokinetic Model for Perfluorooctane Sulfonic Acid (PFOS) and Extension to Perfluorodecanoic Acid (PFDA) at a North American Beef Cattle Farm with a History of Biosolids Land Application
Metal Exposure, Bioaccumulation, and Toxicity Assessment in Sediments from the St. Lawrence River Before and After Remediation Using a Resuspension Technique

Journal Description

Toxics

Toxics is an international, peer-reviewed, open access journal on all aspects of the toxic chemicals and materials, published monthly online by MDPI.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, AGRIS, and other databases.
Journal Rank: JCR - Q1 (Toxicology) / CiteScore - Q1 (Chemical Health and Safety)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.1 days after submission; acceptance to publication is undertaken in 1.9 days (median values for papers published in this journal in the first half of 2025).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.

Impact Factor: 4.1 (2024); 5-Year Impact Factor: 4.6 (2024)

Imprint Information Journal Flyer Open Access ISSN: 2305-6304

Latest Articles

13 pages, 1442 KB

Open AccessArticle

Degradation of Typical PPCPs During Anaerobic Digestion and in Soil

by Min Guo, Linyue Xu, Liguo Guo, Jie Hu and Ru Liu

Toxics 2025, 13(9), 780; https://doi.org/10.3390/toxics13090780 (registering DOI) - 15 Sep 2025

Degradation is a key natural attenuation mechanism governing the fate of PPCPs during anaerobic digestion (AD) and subsequent soil exposure. Nevertheless, the combined impact of this sequential treatment (AD followed by land application) remains poorly understood. This study evaluated the degradation characteristics of [...] Read more.

Degradation is a key natural attenuation mechanism governing the fate of PPCPs during anaerobic digestion (AD) and subsequent soil exposure. Nevertheless, the combined impact of this sequential treatment (AD followed by land application) remains poorly understood. This study evaluated the degradation characteristics of nine PPCPs during mesophilic AD in three distinct soil types. The concentration changes in the nine PPCPs were monitored after 0, 5, 10, 15, 20, 25, and 30 days of anaerobic incubation at 38 °C, as well as after 0, 2, 5, 8, 10, 12, 15, 20, and 30 days of dark incubation at 25 °C with humidity at 75% in three soils. AD effectively removed sulfamethoxydiazine, ciprofloxacin, and oxytetracycline (>80%). The removal efficiencies for carbamazepine, progesterone, triclosan, naproxen, and megestrol acetate were relatively poor, with the removal rates ranging from 50% to 80%, while gemfibrozil exhibited minimal degradation (<50%). The degradation behavior of nine PPCPs fits well with first-order kinetic equations. Calculated half-lives (days) in the three soils were as follows: sulfamethoxydiazine (20.39 to 23.10), carbamazepine (36.48 to 77.02), megestrol acetate (11.18 to 20.39), progesterone (6.08 to 23.90), ciprofloxacin (11.75 to 63.01), oxytetracycline (13.08 to 30.14), naproxen (7.79 to 40.77), gemfibrozil (8.45 to 30.14), and triclosan (14.75 to 46.21). The corresponding R² values ranged from 0.8882 to 0.9320 for sulfamethoxydiazine, 0.8579 to 0.9248 for carbamazepine, 0.8745 to 0.9658 for megestrol acetate, 0.9026 to 0.9560 for progesterone, 0.8147 to 0.9571 for ciprofloxacin, 0.8136 to 0.9063 for oxytetracycline, 0.8961 to 0.9156 for naproxen, 0.8802 to 0.9497 for gemfibrozil, and 0.9099 to 0.9457 for triclosan. Soil physicochemical properties significantly influenced PPCP degradation rates. Gemfibrozil warrants immediate attention due to its poor degradation; the five PPCPs presenting moderate concern—namely carbamazepine, ciprofloxacin, oxytetracycline, naproxen, and triclosan—require further risk assessment, while sulfamethoxydiazine, megestrol acetate, and progesterone pose low persistence risk according to current evidence. Full article

(This article belongs to the Section Emerging Contaminants)

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19 pages, 10863 KB

Open AccessArticle

Effects of ZnFe₂O₄ Nanoparticles on Development and Rhythmic Behavior of Drosophila melanogaster

by Wenhao Yan, Yunfan Guo, Penghui Li, Ziyan Zhang, Jinjun Yang and Yongyan Sun

Toxics 2025, 13(9), 779; https://doi.org/10.3390/toxics13090779 (registering DOI) - 14 Sep 2025

Objectives: This study planned to determine the biological effects associated with ZnFe₂O₄-NPs exposure using Drosophila melanogaster as an in vivo model. Methods: ZnFe₂O₄-NPs were hydrothermally synthesized, and the development of offspring flies were [...] Read more.

Objectives: This study planned to determine the biological effects associated with ZnFe₂O₄-NPs exposure using Drosophila melanogaster as an in vivo model. Methods: ZnFe₂O₄-NPs were hydrothermally synthesized, and the development of offspring flies were evaluated via dietary exposure to different doses of ZnFe₂O₄-NPs (0, 200, 400, 600 μg/mL). Rhythmic behaviors of parent male flies were monitored. Results: Internalization of ZnFe₂O₄-NPs through the intestinal barrier occurred. Oral intake of ZnFe₂O₄-NPs decreased the eclosed adult numbers and perturbed the insect developmental process. In male flies, significant upregulation of HSPs and Turandot family genes was detected, accompanied by ROS reduction and suppressed antioxidant defense responses, and exposure of ZnFe₂O₄-NPs disrupted sleep patterns of males, including a reduction in sleep duration and aggravation of sleep fragmentation. Suppressed activity levels were also found after ZnFe₂O₄-NPs exposure. Significant increased expressions of circadian genes (Clk and Cyc) were detected, alongside elevation of neurotransmitter levels and related gene expressions. Conclusions: Overall, ZnFe₂O₄-NPs can perturb development process via inducing heat shock and detoxification response, and disrupted rhythmic behaviors may be attributed to elevation of neurotransmitter levels and upregulated gene expressions of circadian genes. Our findings may offer valuable insights for evaluating ecological risks of metal-based nanoparticles and suggest potential applications in developing novel pest management strategies by utilizing insect behavioral and physiological responses to nanomaterials. Full article

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17 pages, 560 KB

Open AccessArticle

Nationwide Monitoring and Risk Assessment of Pesticide Residues in Fishery Products

by Dong-ju Kim, Eun-been Oh, Jee-hyo Moon, Jeong-won Choi, Tae-hwa Kim, Seok-hee Lee, Ju-yeon Park, Chan-hyeok Kwon and Kee-sung Kyung

Toxics 2025, 13(9), 778; https://doi.org/10.3390/toxics13090778 (registering DOI) - 14 Sep 2025

Global production of fisheries and aquaculture products continues to increase, with the fisheries sector increasingly considered essential for global food security and nutrition. As public demand for seafood increases, implementation of safety management to minimize risks and ensure the safety of seafood products [...] Read more.

Global production of fisheries and aquaculture products continues to increase, with the fisheries sector increasingly considered essential for global food security and nutrition. As public demand for seafood increases, implementation of safety management to minimize risks and ensure the safety of seafood products becomes important. This study was conducted to monitor 198 chemicals, comprising 161 pesticides and 37 pesticide metabolites, and to assess their risks in saltwater and freshwater fish in the Republic of Korea, based on the analysis of 471 fishery samples (298 saltwater and 173 freshwater). Among the fifteen saltwater fish species analyzed, pesticides were detected in eight species (croaker, flatfish, sea bass, flounder, snapper, yellow tail, salmon, and gizzard shad) and in all seven freshwater species (carp, catfish, crucian carp, eel, leather carp, loach, and trout). Four pesticides (ethoxyquin, lufenuron, metaflumizone, and propiconazole) were detected in saltwater fish, while nine pesticides (ethoxyquin, ipfencarbazone, isoprothiolane, lufenuron, metaflumizone, oxadiargyl, pendimethalin, phoxim, and trichlorfon) were found in freshwater fish. Ethoxyquin was the most frequently detected pesticide in both fish types, mostly in the form of its metabolite, the ethoxyquin dimer. The estimated daily intake (EDI) was calculated based on the maximum concentrations of pesticides detected and the average consumption of fishery products by sex and age group. The hazard quotients, expressed as a percentage of acceptable daily intake (%ADI) and calculated using the EDI and ADI of the pesticides detected, were evaluated to be no more than 5.6%. These results suggest that consumption of saltwater and freshwater fish in the Republic of Korea poses a low risk to human health. This approach can be applied to pesticide residue monitoring and risk assessment in the fisheries sector, providing valuable data for evaluating contamination levels and supporting the regulation and management of chemical residues. Full article

(This article belongs to the Section Agrochemicals and Food Toxicology)

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24 pages, 10678 KB

Open AccessReview

Review of Health Hazards in High-Entropy Alloy Processing Under Laboratory Conditions and Risk Assessment Using a Simple Risk Scoring Model

by Sheetal Kumar Dewangan

Toxics 2025, 13(9), 777; https://doi.org/10.3390/toxics13090777 (registering DOI) - 13 Sep 2025

Certain metal powders used in the synthesis and processing of high-entropy alloys (HEAs) pose significant health hazards, as many of these metals are toxic substances with no biological role in the human body. These metals can mimic essential elements or interfere with metabolic [...] Read more.

Certain metal powders used in the synthesis and processing of high-entropy alloys (HEAs) pose significant health hazards, as many of these metals are toxic substances with no biological role in the human body. These metals can mimic essential elements or interfere with metabolic processes (the chemical reactions in living organisms that sustain life), leading to detrimental health effects. While some metals, such as aluminum, can be eliminated from the body through natural biological processes, others tend to accumulate, causing chronic illnesses over time. This review examines the toxicity mechanisms and health impacts of metals used in HEA synthesis, focusing on laboratory-scale processing. It also identifies potential health risks associated with occupational exposure in laboratory environments, including the inhalation of toxic metal powders and nanoparticles. A simple risk scoring model is introduced to systematically assess and quantify these risks based on factors such as toxicity levels, exposure limits, and carcinogenic potential (the ability of a substance to cause cancer) as given by the Occupational Safety and Health Administration (OSHA) and the National Institute for Occupational Safety and Health (NIOSH) standards. The proposed model can be applied to evaluate the relative hazards of commonly used HEA constituent powders (e.g., Ni, Co, Cr, and Al), offering practical guidance for safer laboratory handling and material selection. By integrating this risk assessment framework, this review aims to enhance workplace safety, guide the development of better material handling practices, and assist researchers in mitigating health risks associated with HEA processing. Full article

(This article belongs to the Special Issue Health Risk Assessment of Exposure to Emerging Contaminants)

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23 pages, 1406 KB

Open AccessReview

Amniotic Fluid and Ocean Water: Evolutionary Echoes, Chemical Parallels, and the Infiltration of Micro- and Nanoplastics

by Antonio Ragusa

Toxics 2025, 13(9), 776; https://doi.org/10.3390/toxics13090776 (registering DOI) - 13 Sep 2025

Background: Abiogenesis is hypothesized to have occurred in the aquatic environments of the early Earth approximately 3.8–4.0 billion years ago, in oceans containing high concentrations of ions (Na⁺ ≈ 470 mmol/L, Cl⁻ ≈ 545 mmol/L, Mg²⁺ ≈ 51–53 mmol/L, Ca [...] Read more.

Background: Abiogenesis is hypothesized to have occurred in the aquatic environments of the early Earth approximately 3.8–4.0 billion years ago, in oceans containing high concentrations of ions (Na⁺ ≈ 470 mmol/L, Cl⁻ ≈ 545 mmol/L, Mg²⁺ ≈ 51–53 mmol/L, Ca²⁺ ≈ 10 mmol/L, K⁺ ≈ 10 mmol/L, SO₄²⁻ ≈ 28–54 mmol/L, HCO₃⁻ ≈ 2.3 mmol/L). Primitive membranes evolved ion-regulatory mechanisms to sustain electrochemical gradients, enabling metabolic activity. Objectives: This review compares the composition of amniotic fluid (AF) to seawater, framing AF as a “biological ocean” for the fetus, and evaluates the impact of micro- and nanoplastics (MNPs) on this protected milieu. Methods: We synthesized data from published studies on concentrations of and ions and other important substances in AF during pregnancy and compared them with marine values. Reports of MNPs detected in placenta, AF, and human organs were systematically reviewed. Results: AF exhibits high ionic similarity to seawater, although the absolute concentrations of ions are lower, reflecting evolutionary conservation. Recent analytical studies identified MNPs in samples of human placenta (4–10 particles per 1 g of tissue), meconium (median 3–5 particles per g), and AF (detectable in >60% of tested samples). Co-exposure to heavy metals, persistent organic pollutants, and endocrine disruptors were reported in 20–40% of maternal–fetal samples. Conclusions: The analogy between oceans and AF underscores a conserved evolutionary continuum. However, the infiltration of MNPs into intrauterine environments is a novel toxicological challenge with potential implications for neurodevelopment, immune programming, and epigenetic regulation. Within the One Health framework, protecting AF from anthropogenic contaminants is as critical as safeguarding marine ecosystems. Full article

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13 pages, 538 KB

Open AccessArticle

Latency Period Among Asbestosis Cases in South Korea by Demographic and Asbestos Exposure Characteristics

by Won Young So, Min-Sung Kang, Young Hwangbo and Mee-Ri Lee

Toxics 2025, 13(9), 775; https://doi.org/10.3390/toxics13090775 (registering DOI) - 13 Sep 2025

Although asbestos use has been banned in many countries, including South Korea, the long latency period of asbestos-related diseases remains a serious public health concern. We conducted a nationwide, registry-based retrospective study to estimate the latency period of asbestosis and identify its determinants. [...] Read more.

Although asbestos use has been banned in many countries, including South Korea, the long latency period of asbestos-related diseases remains a serious public health concern. We conducted a nationwide, registry-based retrospective study to estimate the latency period of asbestosis and identify its determinants. We analyzed exposure history and demographics for 1110 asbestosis cases collected by the Ministry of Environment and the Environmental Health Center for Asbestos in Korea between 2009 and 2021. Mean latency was 45.3 years for asbestosis Grade 1 and 46.3 years for Grade 2. Patients with occupational exposure had shorter latency than those with environmental exposure: 44.4 vs. 46.0 years in Grade 1 (p = 0.010) and 45.0 vs. 47.0 years in Grade 2 (p < 0.001). Within occupations, production-type work showed the shortest latency; within environmental exposure, residence near asbestos-related industries showed the shortest latency, whereas residence near asbestos mines showed the longest. Longer exposure duration (occupational) was associated with shorter latency, and greater residential distance from the source (environmental) with longer latency. Priorities for further investigation include differences by asbestos fiber type and exposure intensity/modality, to inform strengthened occupational health monitoring and targeted surveillance for residents near industrial sources and legacy mines. Full article

(This article belongs to the Section Human Toxicology and Epidemiology)

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17 pages, 1861 KB

Open AccessArticle

Study on Retardation Factors of Cr(VI) Transport in Typical Soils of China

by Xiongbiao Qiao, Xiangyang Zhang, Dejin Zhou, Ning Sun, Zhenyu Ding, Liping Bai and Zongwen Zhang

Toxics 2025, 13(9), 774; https://doi.org/10.3390/toxics13090774 (registering DOI) - 13 Sep 2025

Chromium (VI) mobility in soils critically influenced groundwater contamination risks, but accurate predictions were hindered by the lack of systematic retardation factor (R) data across China’s diverse soils. This study combined Bromide anion (Br⁻)-tracer and Cr(VI) column leaching experiments with CXTFIT [...] Read more.

Chromium (VI) mobility in soils critically influenced groundwater contamination risks, but accurate predictions were hindered by the lack of systematic retardation factor (R) data across China’s diverse soils. This study combined Bromide anion (Br⁻)-tracer and Cr(VI) column leaching experiments with CXTFIT code to determine dispersion coefficients (D) and R values in seven representative Chinese soils (e.g., brown soil, black soil), with model validation against Br⁻ tracer data. By comparing deterministic equilibrium and two-region non-equilibrium models, the research demonstrated that the non-equilibrium approach better characterized Cr(VI) transport, revealing significant soil-dependent R variations (1.09–16.13). Particularly noteworthy was the exceptional Cr(VI) retention observed in Heilongjiang black soil (R > 10), which indicated strong immobilization capacity. As China’s first systematic Cr(VI) retardation database, these findings provided essential parameters for predicting Cr(VI) mobility at contaminated sites, refining risk assessment models, and designing soil-specific remediation strategies—particularly crucial for high-retention regions. Methodologically, this work established an integrated experimental-modeling framework that addressed soil heterogeneity, while its outcomes directly supported regulatory frameworks through updated soil screening values. These findings provided scientific support for formulating region-specific soil management policies, with particular implications for environmental protection and agricultural safety in Cr(VI)-contaminated black soil regions. Full article

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15 pages, 3322 KB

Open AccessArticle

Toxic Effects of BPAF on Marine Medaka (Oryzias melastigma) During Embryo–Larval Stages

by Jiahao Gao, Tianyang Zhou, Zuchun Chen, Ning Zhang, Yusong Guo, Zhongduo Wang, Wenjun Shi and Zhongdian Dong

Toxics 2025, 13(9), 773; https://doi.org/10.3390/toxics13090773 (registering DOI) - 12 Sep 2025

BPAF (Bisphenol AF), one of the primary substitutes for BPA (Bisphenol A), is widely used in the production of plastics, optical fibers, and other materials. During the use of these products, BPAF inevitably enters the environment and exerts toxic effects on animal growth, [...] Read more.

BPAF (Bisphenol AF), one of the primary substitutes for BPA (Bisphenol A), is widely used in the production of plastics, optical fibers, and other materials. During the use of these products, BPAF inevitably enters the environment and exerts toxic effects on animal growth, development, reproduction, immunity, neurology, and genetics. This study employed marine medaka (Oryzias melastigma) as the experimental model to evaluate the toxicological impacts of BPAF on early development. Embryos were exposed to four BPAF concentrations (0, 1 μg/L, 10 μg/L, and 100 μg/L) for 14 days (embryonic to larval stages), followed by phenotypic measurements, behavioral analysis, and gene expression detection. The results demonstrated that BPAF exposure induced developmental malformations and reduced survival rates in marine medaka embryos, with embryo survival negatively correlated with BPAF concentrations. Additionally, BPAF significantly decreased embryonic heart rates, and the 100 μg/L BPAF group exhibited prolonged embryo hatching time and reduced hatching success. In newly hatched larvae, BPAF exposure led to decreased body length, reduced heart rates, and significant suppression of swimming activity, characterized by increased resting time and reduced swimming distance. BPAF exposure altered the expression levels of genes associated with cardiovascular function (e.g., tbx2b, arnt2), the HPT axis (e.g., tg, dio3a, trh, trhr2, tpo), and neurodevelopment (e.g., ache, elavl3, gfap) in the medaka larvae. These transcriptional perturbations are proposed as potential molecular mechanisms underlying the observed phenotypic effects, including reduced heart rates and suppressed swimming behavior in the study. Molecularly, BPAF exposure significantly disrupted the expression of genes related to the cardiovascular system, HPT axis, and nervous system. Full article

(This article belongs to the Special Issue Neurological and Endocrine Impacts of Pollutants on Aquatic Organisms)

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22 pages, 14894 KB

Open AccessFeature PaperArticle

Exposure to Bisphenol S and Bisphenol F Alters Gene Networks Related to Protein Translation and Neuroinflammation in SH-SY5Y Human Neuroblastoma Cells

by Andrea P. Guzman, Christina L. Sanchez, Emma Ivantsova, Jacqueline Watkins, Sara E. Sutton, Christopher L. Souders II and Christopher J. Martyniuk

Toxics 2025, 13(9), 772; https://doi.org/10.3390/toxics13090772 - 12 Sep 2025

Bisphenol A (BPA) replacement chemicals are used in products like food packaging, plastic piping, and sportswear. While they can be toxic, their neurotoxicity is less understood. The aim of this study was to treat differentiated human SH-SY5Y cells with Bisphenol S (BPS) and [...] Read more.

Bisphenol A (BPA) replacement chemicals are used in products like food packaging, plastic piping, and sportswear. While they can be toxic, their neurotoxicity is less understood. The aim of this study was to treat differentiated human SH-SY5Y cells with Bisphenol S (BPS) and Bisphenol F (BPF) to investigate mechanisms of toxicity. BPS reduced cell viability (>50 µM at 48 h) more than BPF (>200 µM at 48 h), with concentration- and time-dependent effects. Both induced caspase 3/7 activity at 250 µM after 48 h, though no changes were observed in levels of reactive oxygen species nor mitochondrial ATPase activity. RNA-seq analysis at 0.1 nM revealed distinct transcriptional networks: BPS altered IL15R, causing NF-kB/NFATC activation, and triggered NF-kB signaling through CD8, while BPF affected TLR9 and activated NF-kB targets through TNF. Pathway analysis showed that genes involved in neuroinflammation, protein folding, microglial function, and motor neuron regulation were disrupted, demonstrating that BPS and BPF, even at low, environmentally relevant concentrations, significantly alter gene expression in pathways linked to neuroinflammation, immune signaling, and neurodegenerative diseases. BPS primarily affected ribosomal and immune-related networks, while BPF disrupted oxidative phosphorylation and protein-folding pathways. These alterations suggest mechanisms for long-term neurological effects, highlighting the need for comprehensive evaluations of BPA alternatives. Full article

(This article belongs to the Section Neurotoxicity)

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19 pages, 708 KB

Open AccessReview

Toxicological Effects of Tartrazine Exposure: A Review of In Vitro and Animal Studies with Human Health Implications

by Malina Visternicu, Alexandra Săvucă, Viorica Rarinca, Vasile Burlui, Gabriel Plavan, Cătălina Ionescu, Alin Ciobica, Ioana-Miruna Balmus, Cristina Albert and Mihai Hogas

Toxics 2025, 13(9), 771; https://doi.org/10.3390/toxics13090771 - 12 Sep 2025

Tartrazine (TZ, also known as FD&C Yellow No. 5 or E102) is a synthetic, water-soluble yellow food dye widely used in the food and pharmaceutical industries. Some studies have associated TZ with allergic reactions, especially among people with dye sensitivities or pre-existing allergies. [...] Read more.

Tartrazine (TZ, also known as FD&C Yellow No. 5 or E102) is a synthetic, water-soluble yellow food dye widely used in the food and pharmaceutical industries. Some studies have associated TZ with allergic reactions, especially among people with dye sensitivities or pre-existing allergies. Recent research also suggests a possible link between TZ consumption and the worsening of behavioral disorders, especially in children, including symptoms such as hyperactivity, irritability, restlessness, and sleep disturbances. Experimental studies in laboratory animals have highlighted potential risks associated with prolonged or high-dose exposure, including toxic effects on the nervous system and liver function. In addition, increasing evidence indicates that TZ can induce oxidative stress (OS) by increasing the production of reactive oxygen species (ROS), which can contribute to cellular damage and inflammation. Although the evidence remains inconclusive, there are recommendations to limit the intake of synthetic food dyes, especially in children’s diets. The purpose of this review is to examine the potential toxic effects on health of tartrazine by analyzing findings from experimental studies in cell cultures and laboratory animals, as well as correlations observed in humans. We focus on documented adverse reactions, including possible neurotoxic, hepatotoxic, oxidative, and behavioral effects. Through this, we aim to contribute to a more comprehensive understanding of the risks associated with exposure to this synthetic food dye. Full article

(This article belongs to the Section Agrochemicals and Food Toxicology)

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14 pages, 1358 KB

Open AccessArticle

Mono(2-ethylhexyl) Phthalate Disrupts Mitochondrial Function, Dynamics and Biogenesis in Human Trophoblast Cells at Human Exposure Range Concentrations

by Luis Daniel Martínez-Razo, Nadia Alejandra Rivero-Segura, Ericka Karol Pamela Almeida-Aguirre, Ismael Mancilla-Herrera, Ruth Rincón-Heredia, Alejandra Martínez-Ibarra and Marco Cerbón

Toxics 2025, 13(9), 770; https://doi.org/10.3390/toxics13090770 - 11 Sep 2025

Mono(2-ethylhexyl) phthalate (MEHP), a bioactive metabolite of di(2-ethylhexyl) phthalate (DEHP), has been detected in the placenta and urine of pregnant women and is linked to adverse pregnancy outcomes. However, its effects on mitochondrial homeostasis in trophoblast cells remain incompletely understood. This study examined [...] Read more.

Mono(2-ethylhexyl) phthalate (MEHP), a bioactive metabolite of di(2-ethylhexyl) phthalate (DEHP), has been detected in the placenta and urine of pregnant women and is linked to adverse pregnancy outcomes. However, its effects on mitochondrial homeostasis in trophoblast cells remain incompletely understood. This study examined the impact of MEHP (0.5–200 µM) on mitochondrial function, dynamics, and biogenesis in human HTR-8/SVneo trophoblast cells. MEHP (≥5 µM) reduced MTT conversion without compromising membrane integrity, suggesting early metabolic or redox imbalance. A dose-dependent loss of mitochondrial membrane potential was observed, with increased reactive oxygen species (ROS) generation only at 200 µM. MEHP modulated the expression of mitochondrial dynamics genes, with a more pronounced mitofusin 1 (MFN1) induction at low doses and increased mitochondrial DNA content, suggesting a compensatory response to mild stress. Conversely, high doses more strongly induced fission and mitochondrial 1 (FIS1) expression, suggesting mitochondrial fragmentation. Both concentrations induced the expression of the mitochondrial biogenesis regulators peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor erythroid 2–related factor 2 (Nrf2), while sirtuin 1 (SIRT1) expression and activity declined progressively with dose. These results demonstrate that MEHP disrupts mitochondrial homeostasis in trophoblast cells at concentrations spanning the estimated human exposure range. The dose-dependent effects, from adaptive responses to overt dysfunction, may help explain the associations between MEHP exposure and placental pathology observed in epidemiological studies. Full article

(This article belongs to the Special Issue Toxicity of Phthalate Esters (PAEs))

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33 pages, 845 KB

Open AccessReview

The Role of Danio rerio in Understanding Pollutant-Induced Gut Microbiome Dysbiosis in Aquatic Ecosystems

by Svetlana G. Frolova, Aleksey A. Vatlin, Iunona Pospelova, Nikita A. Mitkin, Gulnara A. Kulieva and Vsevolod V. Pavshintsev

Toxics 2025, 13(9), 769; https://doi.org/10.3390/toxics13090769 - 11 Sep 2025

Freshwater pollution is a global issue that can impact aquatic organisms in multiple ways. One of the many detrimental consequences of freshwater pollution is the disruption of the intestinal microbiome in aquatic animals. This review addresses the impact of various chemical entities like [...] Read more.

Freshwater pollution is a global issue that can impact aquatic organisms in multiple ways. One of the many detrimental consequences of freshwater pollution is the disruption of the intestinal microbiome in aquatic animals. This review addresses the impact of various chemical entities like pesticides, heavy metals, antibiotics, dyes, and microplastic. Gut microbiota serves as a crucial regulator of metabolic processes across all organisms. Since numerous metabolic pathways are coordinated by microbial communities, even minor disruptions can lead to consequences ranging from mild to severe. The widespread use of chemicals in modern life has made them a primary focus of current gut microbiota research. Zebrafish (Danio rerio) can serve as a model organism to investigate gut microbiome responses to exposure to hazardous contaminants. In this review we include research studying pesticides (methomyl, λ-cyhalothrin, cyproconazole, dieldrin, penthiopyrad, acetochlor, metamifop, imidacloprid, difenoconazole, imazalil, cypermethrin), heavy metals (lead, cadmium, arsenic, chromium, copper, and various nanoparticles), antibiotics (oxytetracycline, florfenicol, doxycycline, trimethoprim, erythromycin, streptomycin, tetracycline, sulfamethoxazole, and clarithromycin), and microplastics (polystyrene, polyethylene, polyester, polypropylene). This review study provides a description of microbiome alterations due to single and combined short- and long-term exposure to the aforementioned contaminants in zebrafish and larvae microbiomes. Full article

(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)

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36 pages, 1537 KB

Open AccessReview

Integrated Approaches of Arsenic Remediation from Wastewater: A Comprehensive Review of Microbial, Bio-Based, and Advanced Technologies

by Aminur Rahman

Toxics 2025, 13(9), 768; https://doi.org/10.3390/toxics13090768 - 10 Sep 2025

Arsenic-containing wastewater and soil systems are a serious hazard to public health and the environment, particularly in areas where agriculture and drinking water depend on groundwater. Therefore, the removal of arsenic contamination from soil, water, and the environment is of great importance for [...] Read more.

Arsenic-containing wastewater and soil systems are a serious hazard to public health and the environment, particularly in areas where agriculture and drinking water depend on groundwater. Therefore, the removal of arsenic contamination from soil, water, and the environment is of great importance for human welfare. Most of the conventional methods are inefficient and have very high operational costs, especially for metals at low concentrations or in large solution volumes. This review delivers a comprehensive approach to arsenic remediation, including microbiological processes, phytoremediation, biochar technologies, bio-based adsorbents, and nanomaterial-assisted techniques. All of these methods are thoroughly examined in terms of removal competence, their mechanisms, environmental impact, cost-effectiveness, and scalability. Phytoremediation and microbial remediation techniques are self-regenerating and eco-friendly, whereas fruit-waste-derived materials and biochar provide abundant adsorbents, and are therefore low-cost. On the other hand, nanotechnology-based approaches show remarkable effectiveness but raise concerns regarding economic feasibility and environmental safety. Additionally, this review represents a comparative analysis and discusses synergistic and hybrid systems that combine multiple technologies for enhancing the remediation performance. Future research directions are emphasized along with challenges such as material stability, regeneration, and policy integration. This review aims to guide decision-makers, research scholars, and industry stakeholders toward affordable, sustainable, and high-performance arsenic remediation techniques for practical use. Full article

(This article belongs to the Special Issue Advances in Remediation of Environmental Pollutants in Soil-Water System)

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15 pages, 10310 KB

Open AccessArticle

ITF6475, a New Histone Deacetylase 6 Inhibitor, Prevents Painful Neuropathy Induced by Paclitaxel

by Guido Cavaletti, Annalisa Canta, Alessia Chiorazzi, Eleonora Pozzi, Valentina Carozzi, Cristina Meregalli, Paola Alberti, Paola Marmiroli, Arianna Scuteri, Luca Crippa, Silvia Fermi, Ibtihal Segmani, Barbara Vergani, Christian Steinkühler and Simonetta Andrea Licandro

Toxics 2025, 13(9), 767; https://doi.org/10.3390/toxics13090767 - 10 Sep 2025

Chemotherapy-induced peripheral neuropathy remains a significant side effect of cancer treatment, often requiring dose reductions or even discontinuation of therapy. Paclitaxel (PTX), a widely used chemotherapeutic agent for solid tumors, is particularly neurotoxic, and no effective treatment exists for paclitaxel-induced peripheral neuropathy (PIPN). [...] Read more.

Chemotherapy-induced peripheral neuropathy remains a significant side effect of cancer treatment, often requiring dose reductions or even discontinuation of therapy. Paclitaxel (PTX), a widely used chemotherapeutic agent for solid tumors, is particularly neurotoxic, and no effective treatment exists for paclitaxel-induced peripheral neuropathy (PIPN). Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone and non-histone proteins, including transcription factors and cytoskeletal components. This study evaluates the HDAC6 inhibitor ITF6475 for its potential to prevent PIPN and compares its effects with ricolinostat, a well-established HDAC6 inhibitor previously studied in cisplatin-induced neuropathy models. Female C57BL/6 mice received PTX vehicle (VEH) or PTX (70 mg/kg intravenously, once per week for four weeks), and the remaining four groups received PTX with co-treatment of either ricolinostat (50 mg/kg orally, daily) or ITF6475 (1, 6, or 12.5 mg/kg orally, daily). Neurophysiological assessments at the end of treatment showed a significant reduction in caudal sensory nerve action potential amplitude across all PTX-treated groups compared to the VEH group. At the same time, PTX treatment led to the development of mechanical allodynia. However, co-treatment with the HDAC6 inhibitor prevented significant differences compared to the VEH group. PTX-induced reduction in intraepidermal nerve fiber density was significantly prevented in the PTX + ITF6475 (1 mg/kg) group, and PTX-induced increase in neurofilament light levels was reduced in all ITF6475 co-treated groups. These findings support the potential of ITF6475 in preventing small fiber damage in a severe, chronic PIPN model. Full article

(This article belongs to the Section Neurotoxicity)

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16 pages, 5953 KB

Open AccessArticle

Proteomics Reveals Mechanisms of Metabolic Dysregulation in Soman Neurotoxicity

by Xing-Xing Zong, Qian Jin, Tong Shi, Ruihua Zhang, Jingjing Shi, Chen Wang and Liqin Li

Toxics 2025, 13(9), 766; https://doi.org/10.3390/toxics13090766 - 10 Sep 2025

Soman, an organophosphorus nerve agent, induces neurotoxicity primarily by inhibiting acetylcholinesterase, triggering a series of pathological events including cholinergic crisis, seizures, calcium overload, oxidative stress, mitochondrial dysfunction, and neuronal death. Nevertheless, the mechanisms underlying metabolic dysregulation—especially after repeated exposure—remain poorly characterized. To address [...] Read more.

Soman, an organophosphorus nerve agent, induces neurotoxicity primarily by inhibiting acetylcholinesterase, triggering a series of pathological events including cholinergic crisis, seizures, calcium overload, oxidative stress, mitochondrial dysfunction, and neuronal death. Nevertheless, the mechanisms underlying metabolic dysregulation—especially after repeated exposure—remain poorly characterized. To address this, we used SWATH-based proteomics to analyze changes in the hippocampal proteome following a repeated soman exposure regimen in a model of hippocampal injury. We identified 38 differentially expressed proteins, predominantly enriched in metabolic pathways. KEGG annotation indicated that these were mainly involved in carbohydrate, amino acid, and lipid metabolism, with specific roles in calcium signaling, tryptophan and tyrosine metabolism, alanine, aspartate and glutamate metabolism, and glyoxylate and dicarboxylate metabolism. Overall, our results demonstrate significant disruption of key metabolic pathways, particularly affecting carbohydrate and amino acid metabolism. We suggest that soman-induced hippocampal damage arises not only from acute calcium overload but also from persistent metabolic dysregulation that impairs energy production and biosynthetic processes. All of our preliminary results shed light on the nature of the biological process and target in the metabolism and provide basic research for the treatment, diagnosis, and prevention of nerve-agent-induced brain damage. Full article

(This article belongs to the Section Neurotoxicity)

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15 pages, 4334 KB

Open AccessArticle

Transcriptome Analyses of Procambarus clarkii (Girard, 1852) Under Individual Exposures to CuSO₄, Pendimethalin, and Glyphosate

by Yao Zheng, Jiajia Li, Zhuping Liu, Ning Wang and Gangchun Xu

Toxics 2025, 13(9), 765; https://doi.org/10.3390/toxics13090765 - 9 Sep 2025

Pesticide usage in the integrated rice–crayfish system has aroused lots of attention all over the world. Especially in China, fish farmers often use copper sulfate and pendimethalin to remove moss from aquaculture water and glyphosate to remove weeds in and around crayfish–crab mixed [...] Read more.

Pesticide usage in the integrated rice–crayfish system has aroused lots of attention all over the world. Especially in China, fish farmers often use copper sulfate and pendimethalin to remove moss from aquaculture water and glyphosate to remove weeds in and around crayfish–crab mixed culture ponds. To explore the stress response mechanism of CuSO₄, pendimethalin, and glyphosate to the hepatopancreas of Procambarus clarkii (Girard, 1852), seven treatment groups including control, CuSO₄ (1 and 2 mg·L⁻¹), pendimethalin (PND, 5 and 10 μg·L⁻¹), and glyphosate (5 and 10 μg·L⁻¹) experimental groups were set up; the transcriptome responses were detected at 4, 8, and 12 days, respectively. The irregular structure and vacuoles were shown in the hepatopancreas for 2 mg·L⁻¹ CuSO₄ and 10 μg·L⁻¹ glyphosate exposures at 12 d, while narrowed hepatic sinusoids were revealed after 10 μg·L⁻¹ pendimethalin exposure. The pathways of ribosome, lysosome, and peroxisome were significantly enriched for differential expression genes (DEGs); in addition, tyrosine metabolism, starch, and sucrose metabolism were enriched under the stress of the three inputs. Genes in related pathways such as glycerophospholipid metabolism, oxidative phosphorylation, and glycerolipid metabolism also changed, and the expression of genes associated with oxidative phosphorylation changed significantly under the stress of the three inputs. Oxidative stress, neurotoxicity, metabolism, and energy supply have been significantly affected by the above herbicide exposure. High concentrations and/or long-term duration exposure may result in metabolic disorders rather than eliminate toxicity through adaptability responses. Full article

(This article belongs to the Section Ecotoxicology)

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27 pages, 2208 KB

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Integrating Experimental Toxicology and Machine Learning to Model Levonorgestrel-Induced Oxidative Damage in Zebrafish

by İlknur Meriç Turgut, Melek Yapıcı and Dilara Gerdan Koc

Toxics 2025, 13(9), 764; https://doi.org/10.3390/toxics13090764 (registering DOI) - 9 Sep 2025

Levonorgestrel (LNG), a synthetic progestin widely used in pharmaceuticals, is increasingly recognized as an emerging aquatic contaminant capable of exerting adverse biological effects beyond endocrine disruption. Acting in a xenobiotic-like manner, LNG may perturb redox homeostasis and induce oxidative stress in non-target species. [...] Read more.

Levonorgestrel (LNG), a synthetic progestin widely used in pharmaceuticals, is increasingly recognized as an emerging aquatic contaminant capable of exerting adverse biological effects beyond endocrine disruption. Acting in a xenobiotic-like manner, LNG may perturb redox homeostasis and induce oxidative stress in non-target species. To elucidate these mechanisms, this study integrates experimental toxicology with supervised machine learning to characterize tissue-specific and dose–time related oxidative responses in adult Zebrafish (Danio rerio). Fish were exposed to two environmentally relevant concentrations of LNG (0.312 µg/L; LNG-L and 6.24 µg/L; LNG-H) and a solvent control (LNG-C) for 24, 48, and 96 h in triplicate static bioassays. Redox biomarkers—superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA)—were quantified in liver and muscle tissues. LNG-H exposure elicited a time-dependent increase in SOD activity, variable CAT responses, and a marked elevation in hepatic GPx, with sustained MDA levels indicating persistent lipid peroxidation. Five classification algorithms (Logistic Regression, Multilayer Perceptron, Gradient-Boosted Trees, Decision Tree and Random Forest) were trained to discriminate exposure outcomes based on biomarker profiles; GBT yielded the highest performance (96.17% accuracy), identifying hepatic GPx as the most informative feature (AUC = 0.922). Regression modeling via Extreme Gradient Boosting (XGBoost) further corroborated the dose- and time-dependent predictability of GPx responses (R² = 0.922, MAE = 0.019). These findings underscore hepatic GPx as a sentinel biomarker of LNG-induced oxidative stress and demonstrate the predictive utility of machinelearning-enhanced toxicological frameworks in detecting and modeling sublethal contaminant effects with high temporal resolution in aquatic systems. Full article

(This article belongs to the Special Issue Computational Toxicology: Exposure and Assessment)

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26 pages, 3368 KB

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Effects of Gossypol Exposure on Ovarian Reserve Function: Comprehensive Risk Assessment Based on TRAEC Strategy

by Xiaoyan Sun, Jia Ying, Xuan Ma, Yunong Zhong, Ran Huo and Qingxia Meng

Toxics 2025, 13(9), 763; https://doi.org/10.3390/toxics13090763 - 9 Sep 2025

This study evaluated the reproductive toxicity and reversibility of gossypol exposure in female Institute of Cancer Research (ICR) mice using the Targeted Risk Assessment of Environmental Chemicals (TRAEC) framework. Mice treated with gossypol (20 mg/kg/day, 30 days) showed reduced body weight (35.90 ± [...] Read more.

This study evaluated the reproductive toxicity and reversibility of gossypol exposure in female Institute of Cancer Research (ICR) mice using the Targeted Risk Assessment of Environmental Chemicals (TRAEC) framework. Mice treated with gossypol (20 mg/kg/day, 30 days) showed reduced body weight (35.90 ± 3.19 g vs. 30.26 ± 0.91 g, p < 0.001), depletion of primordial follicles (46.2 ± 4.8 vs. 27.5 ± 3.6, p < 0.01), and impaired oocyte maturation, with polar body extrusion decreasing from 65.9% to 22.6% at 60 μM (p < 0.0001). In the human granulosa-like tumor cell line (KGN), apoptosis increased to 91.1% at 20 μg/mL compared with 11.46% in controls (p < 0.0001). Proteomic profiling identified 151 differentially expressed proteins, enriched in steroidogenesis, immune regulation, and mitochondrial metabolism. After one-month withdrawal, partial morphological recovery was observed, but endocrine function remained impaired. The TRAEC risk score of 4.68 classified gossypol as a moderate reproductive toxicant. These findings indicate that gossypol damages ovarian reserve and oocyte competence, with only partial reversibility, highlighting the need for caution in its clinical use. Full article

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18 pages, 3365 KB

Open AccessArticle

Assessing Multiple Risks in Regulating Reservoirs: Perspectives on Heavy Metal Contamination

by Hui Zhou, Zhiping Li, Anming Wang, Jiawei Zhu, Zongyuan Han, Yalin Zhang and Dongdong Chen

Toxics 2025, 13(9), 762; https://doi.org/10.3390/toxics13090762 (registering DOI) - 8 Sep 2025

As the terminal reservoir of the South-to-North Water Diversion’s Eastern Route, Dongping Lake is critical for safeguarding the northern water supply. Analysis of 33 water–sediment sites revealed the following. (1) Waterborne heavy metals (HMs) below WHO limits, confirming the good water quality. (2) [...] Read more.

As the terminal reservoir of the South-to-North Water Diversion’s Eastern Route, Dongping Lake is critical for safeguarding the northern water supply. Analysis of 33 water–sediment sites revealed the following. (1) Waterborne heavy metals (HMs) below WHO limits, confirming the good water quality. (2) Sediment HM enrichment exceeding background levels, with Cd posing high ecological risk (mean E_r = 135), and moderate overall pollution. (3) Speciation showed V, Cr, Co, Ni, Cu, Zn, and Pb predominantly in residual fractions, while Cd exhibited high bioavailability and Pb was in reducible state. Ecological risk assessment indicated that V and Cr tend not to cause environmental pollution; Co, Ni, Cu, Zn, and Pb only cause slight pollution; and Cd causes serious point-source pollution. The carcinogenic risk of surface sediments to children is not negligible. (4) Source apportionment identified industrial emissions as the primary HM contributors, with Cd deriving from agricultural runoff (phosphate fertilizers) and industrial discharges. This study offers valuable baseline information for water quality management in mega-water-transfer projects, directly supporting the Jiaodong Main Line and Yellow River Crossing operations. Full article

(This article belongs to the Section Metals and Radioactive Substances)

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21 pages, 1135 KB

Open AccessArticle

Measuring Environmental Chemical Burden with Wristbands: Implications for Kidney Health Among Women in Rural Guatemala

by Jaime Butler-Dawson, Grant Erlandson, Diana Jaramillo, Karely Villarreal Hernandez, Laura Calvimontes, Lyndsay Krisher, Miranda Dally, Stephen Brindley, Daniel Pilloni, Alex Cruz, Alison K. Bauer, Richard J. Johnson, Lee S. Newman, Joshua Schaeffer, John L. Adgate, Kim A. Anderson and Katherine A. James

Toxics 2025, 13(9), 761; https://doi.org/10.3390/toxics13090761 - 8 Sep 2025

Chronic kidney disease of unknown origin (CKDu) is a public health concern, particularly in agricultural communities, with multiple environmental exposures hypothesized as potential contributors. This study employed a targeted exposure assessment using personal silicone wristbands to characterize chemical exposures among women living and [...] Read more.

Chronic kidney disease of unknown origin (CKDu) is a public health concern, particularly in agricultural communities, with multiple environmental exposures hypothesized as potential contributors. This study employed a targeted exposure assessment using personal silicone wristbands to characterize chemical exposures among women living and working in CKDu-affected regions of Guatemala. Participants wore wristbands for seven days, passively sampling air and dermal exposures. Overall, 45 wristbands were collected from 37 female participants (19 sugarcane workers and 18 community members). Of the 1530 chemicals measured using a single semi-quantitative method, 103 were detected, with an average of 27 chemicals per wristband (range: 16–40). Polycyclic aromatic hydrocarbon (PAH) levels were higher in community members’ wristbands, whereas workers exhibited higher exposure to pesticides (i.e., pendimethalin and fipronil). Workers had worse kidney function compared to community members, with almost half of the workers having an estimated glomerular filtration rate, eGFR, <90 mL/min/1.73 m². Correlations were observed between kidney function markers and specific chemicals, with the strongest correlation between albumin-to-creatinine ratio and pyrene levels (ρ = 0.57, p < 0.01) among workers. Women in agricultural regions of Guatemala experience widespread exposure to diverse environmental chemicals, some of which may contribute to kidney function decline. Full article

(This article belongs to the Special Issue Exposure to Chemicals and Health Effects in Occupational and Everyday Settings)

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